tbuckley/cabot-search huggingface dataset:
Predicting early mortality and overall survival (OS) in acute promyelocytic leukemia (APL) based on Charlson comorbidity index (CCI).
Authors: Prajwal Dhakal, Elizabeth Lyden, Avantika Pyakuryal, Vijaya Raj Bhatt
Journal: Journal of Clinical Oncology (2022)

e19017 Background: CCI is an established tool used to measure the comorbidity burden in patients, with higher CCI signifying a greater comorbidity burden. We performed a large database analysis to evaluate CCI as a predictor of one-month mortality and OS in patients &lt; 60 years with APL. Methods: Using the National Cancer Database, we identified a total of 4969 patients &lt; 60 years diagnosed with APL between 2004 and 2015. We divided patients into 3 groups with CCI of 0, 1, and ≥2. Multiple regression analysis was used to evaluate the effects of CCI on one-month mortality. Cox regression model determined the impact of CCI on OS. Results: Seventy-eight percent of patients had CCI of 0; 16% had CCI 1, and 6% had CCI ≥2. Median age was 42 years (range 0-59), and patients 41-59 years comprised 53% of the total cohort. Fifty-one percent were female, 32% were treated at academic centers, and 67% had private insurance. One-month mortality was 5%, 14%, and 25% for patients with CCI 0, 1 and ≥2, respectively. After adjusting for other co-variates, one-month mortality was worse for patients with CCI 1 (Odds ratio 2.6, 95% confidence interval [CI] 2.0-3.4, p &lt; 0.001) and CCI ≥2 (Odds ratio 5.3, 95% CI 3.9-7.4, p &lt; 0.001) compared to patients with CCI 0. Median 5-year OS was 85%, 71%, and 60% for patients with CCI 0, 1, and ≥2, respectively. After adjusting for other co-variates, OS was worse for patients with CCI 1 (Hazard ratio [HR] 1.8, 95% CI 1.5-2.1, p &lt; 0.001), and CCI ≥2 (HR 2.7, 95% CI 2.2-3.3, p &lt; 0.001) compared to patients with CCI 0. Patients 41-59 years had worse OS than 0-18 years (HR 2.4, 95% CI 1.3-4.5, p = 0.003). Private insurance was associated with better OS than Medicare (HR 2.1, 95% CI 1.7-2.6, p &lt; 0.001) and Medicaid/other government insurance (HR 1.3, 95% CI 1.1-1.6, p &lt; 0.001). Conclusions: This is one of the first and the largest database analyses examining the prognostic association of comorbidity burden in younger patients with APL. CCI independently predicted both one-month mortality and OS. Compared to CCI of 0, one-month mortality increased by 2.5-fold with CCI 1 and more than five-fold with CCI ≥2. The higher chances of one-month mortality in patients with greater comorbidity burden may reflect the risks associated with initial APL diagnosis and treatment such as coagulopathy, infection, and differentiation syndrome. One-month mortality was the key driver for OS. OS was also worse among patients with higher CCI. Our results indicate CCI as an important predictor of one-month mortality and OS in APL. CCI should be taken into consideration while interpreting clinical trial results.
Democratizing germline genetic testing and its impact on prostate cancer clinical decision-making.
Authors: Neal D. Shore, Mukaram Gazi, Christopher Michael Pieczonka, Sean Heron, David J Cahn, Laurence Belkoff, Aaron D. Berger, Brian Mazzarella, Joseph Veys, David Morris, Alexander Engelman, Paul Dato, Richard Bevan-Thomas, Robert Cornell, Paige Layman, Kathryn E. Hatchell, Brandie Heald, Sarah M. Nielsen, Robert Luke Nussbaum, Edward D. Esplin
Journal: Journal of Clinical Oncology (2022)

10500 Background: Approximately 10-15% of prostate cancer (PCa) patients (pts) have a pathogenic germline variant (PGV). Identification of a PGV has important implications affecting decisions regarding cancer screening, treatment selection, and family cascade testing. There exists limited data documenting real world recommendations post germline genetic testing (GGT). This study was designed to collect clinician reported outcomes from PCa pts who underwent GGT. Methods: An IRB-approved, nationwide, prospective registry recruited unselected PCa pts from 15 community and academic urology practices. Pts underwent an 84-gene panel test, with clinical outcomes collected via clinician-completed case report forms &gt; 1-month post GGT. Statistical significance was determined by two-tailed Fisher’s exact test. Results: 982 predominantly white (75.9%), non-metastatic (80.7%) males with PCa were recruited; 56.9% met National Comprehensive Cancer Network (NCCN) GGT criteria. Average age was 65.3 years at PCa diagnosis. PGVs, most commonly CHEK2 (17) and BRCA2 (10), were identified in 100 (10.2%) pts; 34 (34%) of these did not meet NCCN GGT criteria. Among PGV positive pts, 241 recommendations were made (Table). They were more likely to have changes to treatment (p &lt; 0.0001), follow up (p &lt; 0.0001) and cascade testing recommendations (p &lt; 0.0001) than those with negative/variant of uncertain significance (VUS) results. There were no significant differences in changes to treatment (p = 0.4471) or follow up (p = 0.861) for pts who met NCCN criteria versus those who did not. 7 pts with PGVs received targeted therapy or were referred to a clinical trial. 5 pts with VUS results were also referred to a clinical trial. Among these 12 pts, 6 (50%, 2 CHEK2 PGV, 1 ATM PGV, 1 VUS each ATM, BLM, CHEK2) did not meet NCCN GGT criteria. Referral to a genetic counselor was the most common follow up recommendation for those with PGV (38 patients, 38%) and VUS results (66, 13.7%). The most commonly reported impact to health outcomes for those with negative results was knowledge/reassurance (38, 7.88%). Conclusions: This study showed that GGT did influence PCa pts care. Appropriately, pts with PGVs received a greater number of recommendations for relatives, changes to follow up and treatment. [Table: see text]
TBIO-08. The molecular basis for rational targeting of FGFR-driven growth and invasiveness in pediatric brain tumors
Authors: Jessica Migliavacca, Karthiga Santhana Kumar, Levi Kopp, Alexandre Gries, Shen Yan, Cyrill Brunner, Matthias Schuster, Simon Jurt, Kerstin Moehle, Oliver Zerbe, Gisbert Schneider, Michael Grotzer, Martin Baumgartner
Journal: Neuro-Oncology (2022)

Abstract The oncogenic activation of receptor tyrosine kinases (RTK) promotes growth, survival and dissemination in pediatric tumors including glioma, ependymoma and medulloblastoma (MB). Direct targeting of either the RTK or of downstream kinases can effectively block tumor promoting pathway functions. However, emergence of resistance is common. We hypothesized that alternative interference strategies that target protein-protein interactions (PPIs) instead of enzymatic activities could overcome the emergence of resistance. We characterized the molecular interactions downstream of the FGFR that regulate relevant growth and invasion-promoting mechanisms in MB cells, to identify potentially druggable PPIs. We found that the FRS2 protein is an essential up-stream effector of FGFR signaling towards invasiveness. Using a proteomics approach, we furthermore identified the Striatin 3 protein as a novel oncogenic effector of the FGFR pathway downstream of FRS2, as it integrates antagonistic growth and invasion signals downstream of FGFR. Mechanistically, Striatin 3 interacts with the Ser/Thr kinase MAP4K4, couples it to the protein phosphatase 2A, and thereby inactivates growth repressing activities of MAP4K4. In parallel, Striatin 3 enables MAP4K4-mediated phosphorylation of PKC-theta and VASP, which combined are necessary to promote tissue invasion. To selectively repress pro-invasive FGFR functions, we identified and functionally validated small molecule ligands of FRS2, that prevent FRS2 activation and downstream signaling. We demonstrate efficacy of these compounds in inhibiting invasion and growth promoting activities in vitro and in vivo, and identified potential off-target activities of the ligand using a proteome-wide interaction analysis. We propose inhibition of FRS2 by a small molecular PTB domain ligand as a strategy to repress FGF signaling in FGFR-driven tumors. The development of this ligand, and the de novo design of functional analogs thereof bear promise for further pre-clinical evaluation of these structures as anti-growth promoting and anti-metastatic therapeutics applicable to FGFR-driven tumors.
QOL-24. Evaluating the diagnostic validity &amp; predictive value of the Cerebellar Cognitive Affective Syndrome (CCAS) in pediatric posterior fossa tumour patients
Authors: Doris Hoffmann-Lamplmair, Ulrike Leiss, Andreas Peyrl, Irene Slavc, Thomas Czech, Alexandra Gram, Thomas Pletschko
Journal: Neuro-Oncology (2022)

Abstract OBJECTIVE: The present study aimed to examine the extent of deficits associated with the Cerebellar Cognitive Affective Syndrome (CCAS) in patients treated for paediatric posterior fossa tumours (PFT). Furthermore, we wanted to assess its diagnostic validity and predictive value for late sequelae. METHOD: Neuropsychological test data from 56 PFT patients treated at our pediatric neuro-onocology unit (mean age at treatment: seven years; mean age at first neuropsychological examination: nine years) were examined for severity of deficits in the CCAS core domains of executive functions, verbal functions, visuospatial abilities and emotions/behaviour. Patients with CCAS (n=20) were compared to two control groups without the syndrome (PFT patients treated either surgically (n=18) or surgically followed by radio/chemotherapy (n=18)) in terms of long-term neuropsychological and educational outcomes (mean age: 14 years). We also examined risk factors for CCAS development. RESULTS: The results showed mild to severe impairment in at least one CCAS domain in 55 out of 56 patients. Complete CCAS was diagnosed in 35.7% of cases. Seven years after tumour diagnosis, information processing, logical thinking, verbal functions, visuospatial skills and executive functions were more impaired in CCAS patients than in controls. They also needed more special educational support. Information processing speed was equally poor in CCAS patients and in controls treated with chemotherapy/radiotherapy. A significant association was found between risk factors and deficits in information processing speed, but not with the occurrence of CCAS. CONCLUSION: Deficits in the central CCAS features are common in PFT patients, but in varying degrees, suggesting that it is a continuous syndrome rather than a dichotomous one. However, it is problematic that domains such as information processing speed are not included in the diagnosis. External criteria regarding everyday life should be considered in future studies.
Improving understanding of pancreatic cancer among patients using an animated patient’s guide to benefit informed decisions and health outcomes.
Authors: Satish Munigala, Eileen Mary O'Reilly, David E Bakelman, Jane Holt, Andrew H. Ko, Nicholas Searle, Andres Gelrud
Journal: Journal of Clinical Oncology (2022)

e16282 Background: Pancreatic cancer (PC) outcomes continue to be dismal in the United States with an estimated 48,220 deaths in 2022. Patients have limited knowledge regarding their management options making informed decisions difficult. Health literacy (HL) is a major barrier confronting patient understanding and visual formats of learning have been shown to help overcome HL barriers to enable informed patient understanding. Effective PC learning resources can mitigate poor disease understanding, and reduce HL impediments essential to patient decisions and best outcomes. In this study, we evaluated patient knowledge improvement, engagement, and participation in decisions with their oncology providers using National Pancreas Foundation’s (NPF) ‘An Animated Patient’s Guide to Pancreatic Diseases (APG)’ . Methods: NPF introduced APG in 2013, as an educational resource to address patient needs, informed decisions, barriers to HL and gaps in understanding. Using visual formats of learning (animations, videos, slide shows), we monitored metrics and learner feedback from September, 2013 to September 2021 (8 years). We evaluated learner activity, number of views with highest retention in the US and globally. Results: We gathered learner data on APG from 4,551,079 learners from over 100 countries. Most learners (60%) were from the US with 54% being patients, 17% family/caregivers, 16% healthcare providers and 13% other. The top 3 animations “ Understanding Clinical Trials”, “ Pancreatic Cancer: Treatment and Outcomes”, and “ Pancreatic Cancer: Signs, Symptoms and Risk Factors” had 182,217; 82,585; and 64,970 viewings respectively. Top 3 expert videos viewed most were “ What are the different stages of pancreatic cancer?”, “ What are the symptoms of pancreatic cancer?”, and “ What is a “Placebo” in a clinical trial and is it always used?" with 15,357; 12,475; and 5,282 views respectively. Conclusions: Our study shows that visual formats of education provided by APG were effective in improving patient understanding, enabling informed decisions, and addressing needs of PC patients with poor understanding and HL. Pancreatic cancer education utilizing visual formats has great potential to provide effective learning for patients. Continued efforts should be made to address HL barriers, inform patients, and provide resources that address needs in PC to achieve best healthcare outcomes.
Prognostic value of PIOS (Patras Immunotherapy Score) model in patients with advanced NSCLC treated with combination of immunotherapy with chemotherapy: Preliminary results from a European retrospective study.
Authors: Foteinos-Ioannis D. Dimtrakopoulos, Petros Christopoulos, Mariam Elshiaty, Lea Daniello, Ioannis Pyrousis, Anastasia E Kottorou, Thomas Makatsoris, Haralabos Kalofonos, Angelos Koutras
Journal: Journal of Clinical Oncology (2022)

e21096 Background: Ιmmune checkpoint inhibitors (ICIs) have tremendously changed the daily clinical practice on the treatment of advanced non-small cell lung cancer (aNSCLC). However, clinical useful biomarkers remain an unmet need. Recently, a new score, Patras Immunotherapy Score (PIOS), has been proposed by our group proving its prognostic value in aNSCLC patients treated with ICIs monotherapy. The objective of the current study was to assess the clinical significance of PIOS formula in aNSCLC patients treated with combination of immunotherapy with chemotherapy. Methods: PIOS is a baseline formula derived by combining the following non-interventional clinical parameters, Performance Status (PS), Body Mass Index (BMI), age and Line Of Treatment (LOT) and it is calculated as PIOS = (PS×BMI)/(LOT×AGE). In the current study, 159 aNSCLC patients, treated with combination of immunotherapy with chemotherapy, were retrospectively selected, blindly to the clinical outcome, and enrolled. In addition, a second subcohort with 444 aNSCLC patients, who had been treated with chemotherapy alone, were also retrospectively included. The primary endpoint of this study was to investigate the prognostic value of PIOS in terms of progression free survival (PFS) and overall survival (OS). Results: Patients with higher PIOS score had longer PFS compared to patients with lower PIOS score (ΗR 0.575, 95% CI 0.364-0.908, p= 0.016), while multivariate analysis for PFS, adjusted for PD-L1, confirmed the clinical value of PIOS score (HR 0.561, 95% CI 0.352-0.893, p= 0.015). Moreover, PIOS score was also associated with prognosis ( p= 0.003). The median OS for the favorable group was 1067 days compared to 528 days for the unfavorable group with low PIOS score (HR 0.487, 95% CI 0.302-0.787, p&lt; 0.001) at univariate analysis. This association remained statistically significant (HR 0.468, 95% CI 0.286-0.764, p= 0.002) after adjusting for PD-L1 expression. Specificity of PIOS formula was also confirmed in the second cohort (n = 444) of patients with metastatic disease who had been treated with chemotherapy alone, in which no prognostic significance for PIOS was observed. Conclusions: This study for the first time documents the prognostic significance of PIOS model in aNSCLC patients treated with immunotherapy/chemotherapy combination and provides adequate evidence regarding the specificity of this association, since no similar finding was observed in the patients treated with chemotherapy alone.
Efficacy and safety of initial five years of adjuvant endocrine therapy in postmenopausal hormone receptor-positive breast cancer: A systematic review and network meta-analysis.
Authors: Hao Liao, Jianxin Zhong, Wendi Pei, Shao Bin, Xiao-ran Liu, Hope S. Rugo, Huiping Li
Journal: Journal of Clinical Oncology (2022)

535 Background: Endocrine therapy has greatly improved the clinical outcomes of hormone receptor-positive breast cancer patients. However, there was an unmet need to identify the potentially best regimen of initial adjuvant endocrine therapy. Therefore, in this network meta-analysis, we synthesized the latest evidence to indirectly compare the efficacy and safety among different 5 years of regimens of initial adjuvant endocrine therapy. Methods: We conducted a systematic search of the PubMed, Web of Science, and EMBASE in January 2022. Randomized clinical trials assessing the efficacy and safety of initial 5 years of adjuvant endocrine therapy were included. The primary outcomes were disease-free survival (DFS) and overall survival (OS) and the secondary outcome was severe adverse effects (SAEs). A Bayesian network meta-analysis was carried out to indirectly compare all regimens and the SUCRA values were used to obtain rankings. Results: Eleven studies with 49,987 subjects were included. For DFS, exemestane (EXE) (hazard ratio [HR] 0.91, 95% confidence interval [95%CI] 0.87-0.96), anastrozole (ANA) (0.94, 0.90-0.97), letrozole (LET) (0.93, 0.89-0.97), tamoxifen (TAM) followed by EXE (0.91, 0.87-0.96), and TAM followed by ANA (0.92, 0.87-0.98) were more favorable than TAM, with TAM followed by EXE ranking as the first of SUCRA. For OS, only TAM followed by ANA showed significant superiority than TAM (HR 0.91, 95%CI 0.86-0.97) and ranked as the first of SUCRA. For SAEs, EXE (HR 1.72, 95%CI 1.04-2.98), ANA (1.58, 1.03-2.43), and LET (1.63, 1.02-2.57) showed greater associations with bone fracture than TAM. However, no significant difference in the incidences of cardiac events, thromboembolic events, and cerebrovascular events was found among all comparisons. Conclusions: The sequential use of aromatase inhibitors may be the optimal treatment mode for hormone receptor-positive postmenopausal early breast cancer patients. In addition, the three kinds of aromatase inhibitors achieved roughly equal efficacy, but caused different types of SAEs.
A survey on gene mutations of PD-1/PD-L1 treatment in Chinese lung cancer patients.
Authors: Fang Fang Long, Wen Chuang Huang, Bo Peng, Jing Zhang, Suo Peisu, Shifu Chen, Fa Sheng Wu
Journal: Journal of Clinical Oncology (2022)

e20503 Background: The expression of PD-L1 is closely related to the curative effect. Here, we want to study the details of gene mutation in expression and dig out some relevant information from Chinese LC patients. Methods: LC patients with both genomic information and PD-L1 expression status were screened from HapLab database. PD-L1 expression was detected by immunochemistry. R packages ClusterProfiler was used for gene enrichment analysis. Results: LC Patients were divided into two groups by tumor proportion score (TPS):1039 PD-L1 negative patients (TPS &lt; 1%) and 1669 PD-L1 positive patients (TPS &gt; = 1%). The overall mutation frequency of 51 genes were significantly different between PD-L1 negative patients and PD-L1 positive patients (Chi-Squared test, Pvalue &lt; 0.05). 6 genes were mutated at high frequencies in patients with high TPS, and 45 genes were mutated at high frequencies in patients with low TPS. Among these genes, FGFR3, MDM2 and SKT11 have been reported to be associated with HPD, showing significantly higher mutation frequencies in PD-L1 negative patients (Pvalue &lt; = 0.001). Two sets of genes were enriched respectively, both of which were enriched in MAPK and PI3K-Akt related pathways, while the enrichment results of EGFR tyrosine kinase inhibitor resistance only existed in PD-L1 negative. Conclusions: Our study investigated the genomic alterations associated with PD-L1 expression status in Chinese LC patients. From the data of Chinese lung cancer patients, we found 55 genes related to PD-1/PD-L1 treatment. These genes contain HPD related genes. Perhaps PD-L1 expression is associated with HPD.
Reappraisal of the treatment duration of antibiotic regimens for acute uncomplicated cystitis in adult women: A systematic review and network meta-analysis of 61 randomised clinical trials
Authors: K. Do Kyung, K. Jae Heon, L. Joo Yong, K. Nam Su, L. Hye Sun, P. Ju-Young, K. Jong Won, C. Kang Su
Journal: European Urology (2022)
Assessment of changes in arterial blood pressure after nephrectomy for kidney cancer: VAPANCR (UroCCR 26)_prospective study
Authors: P. Bigot, J-C. Bernhard, N. Doumerc, F-X. Nouhaud, I. Ouzaid, P. Saulnier, A. Mejean, M. Roupret, K. Bensalah
Journal: European Urology (2022)
DIPG-36. The brain-gut-microbiota axis to predict outcome in pediatric diffuse intrinsic pontine glioma
Authors: Loris De Cecco, Veronica Biassoni, Elisabetta Schiavello, Andrea Carenzo, Maria Federica Iannò, Armando Licata, Manuela Marra, Maria Carollo, Luna Boschetti, Maura Massimino
Journal: Neuro-Oncology (2022)

Abstract OBJECTIVE: Diffuse intrinsic pontine glioma (DIPG) is a rare childhood brain tumour with poor prognosis. Radiotherapy (RT) remains the only palliative intervention. In this scenario, it is essential to investigate tumor and patient microinvironment. Microbiota plays a critical role in human health and a functional link between the central nervous system and gut microbiota has been reported: the microbiota-gut-brain axis. With these premises, we have investigated the gut microbiota in DIPG. METHODS: A cohort of 18 patients was enrolled and we collected stool specimens at diagnosis (pre-RT) and after radiotherapy. Microbiota content was analysed through 16S rRNA sequencing on IONS5xl; base calling and demultiplexing were performed by Torrent Suite (ThermoFisher). Association to progression free survival (PFS) and overall survival (OS) were assessed by cox-regression univariate analyses and differential abundance (DA) analyses identified differences following RT. RESULTS: The Firmicutes/Bacteroidetes (F/B) ratio in pre-RT specimens has a median of 0.757 (range= 0.243-1.19). Having PFS as endpoint and at family classification level, an increased risk of disease progression was disclosed for Flavobacteriaceae and Bacillales with HR of 1.57 (p=0.00913) and 1.57 (p=0.215), respectively. The anaerobic bacteria Synergistaceae is found related to a decreased risk of progression with HR 0.662 (p=0.00718). These findings were also confirmed with OS as endpoint. DA analyses pointed out a number of families belonging to Firmicutes and Bacteroidetes phyla highly differentiated (log2|fold-change|&amp;gt;2) between pre- and post-RT. CONCLUSIONS: This study represents the first report of the microbiota-gut-brain axis role in DIPG patients. The F/B ratio, a parameter of normal intestinal homeostasis, show the presence of inflammatory patterns and some family members are associated to increased disease progression. These preliminary findings needs further validations. However, 16S microbiota has the potential ability to stratify patients and probiotic administration could restore a normal F/B ratio.